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1.
J Formos Med Assoc ; 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32591157

RESUMO

PURPOSE: In advanced or high-grade prostate cancer (PCa), prostate-specific antigen (PSA) is usually elevated, however, some patients may present with low initial PSA (iPSA) levels. The objective of this study was to evaluate whether different iPSA levels were associated with dissimilar clinical outcomes among men with high-grade PCa and advanced disease after robot-assisted laparoscopic radical prostatectomy (RaLRP). METHODS: This study enrolled 69 PCa patients with initial Gleason score ≥8 and pathologic T-stage ≥3a from April 2012 to December 2018. Patients were stratified into 3 groups based on iPSA levels at diagnosis: <5.0, 5.0-9.9, and ≥10.0. The patients' related parameters were compared among these groups. RESULTS: The median follow-up period was 33.1 months (IQR: 12.1-48.1). There was no difference in biochemical recurrence (BCR) between the 3 groups (Log-rank test, p = 0.484). We found a higher risk of biochemical recurrence in patients with positive surgical margins (HR: 5.04, 95% CI: 1.64-15.50, p = 0.005). In addition, patients with low iPSA levels (<5.0 ng/mL) had poor radiographic progression-free survival (Log-rank test, p = 0.001) and a higher risk of disease progression (HR: 12.2, 95% CI: 1.18-1260.99, p = 0.036) compared with patients with higher iPSA levels (≥10 ng/mL). CONCLUSION: In patients with high-grade locally-advanced PCa, a low iPSA level was associated with a higher risk of disease progression, but not with biochemical recurrence. In this unique population, serum PSA may not be a reliable marker to detect disease progression. Monitoring of these patients may warrant other biomarkers or imaging.

2.
Rev Bras Ter Intensiva ; 32(1): 123-132, 2020 Mar.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32401985

RESUMO

OBJECTIVE: To report on the currently available prediction models for the development of acute kidney injury in heterogeneous adult intensive care units. METHODS: A systematic review of clinical prediction models for acute kidney injury in adult intensive care unit populations was carried out. PubMed® was searched for publications reporting on the development of a novel prediction model, validation of an established model, or impact of an existing prediction model for early acute kidney injury diagnosis in intensive care units. RESULTS: We screened 583 potentially relevant articles. Among the 32 remaining articles in the first selection, only 5 met the inclusion criteria. The nonstandardized adaptations that were made to define baseline serum creatinine when the preadmission value was missing led to heterogeneous definitions of the outcome. Commonly included predictors were sepsis, age, and serum creatinine level. The final models included between 5 and 19 risk factors. The areas under the Receiver Operating Characteristic curves to predict acute kidney injury development in the internal validation cohorts ranged from 0.78 to 0.88. Only two studies were externally validated. CONCLUSION: Clinical prediction models for acute kidney injury can help in applying more timely preventive interventions to the right patients. However, in intensive care unit populations, few models have been externally validated. In addition, heterogeneous definitions for acute kidney injury and evaluation criteria and the lack of impact analysis hamper a thorough comparison of existing models. Future research is needed to validate the established models and to analyze their clinical impact before they can be applied in clinical practice.

3.
Sci Rep ; 10(1): 6640, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32313131

RESUMO

Our study showed that total urinary arsenic concentrations were positively correlated with renal cell carcinoma (RCC). Chronic inflammation is a key player in the development of RCC. This study explored the association between nucleotide-binding domain-like receptor protein 3 (NLRP3) genotypes and the development of RCC. We also investigated whether any of the NLRP3 genotypes modified the risk between arsenic and RCC. We recruited 350 RCC patients and 700 age-sex matched controls. RCC was confirmed by pathological assessment following surgical resection or image-guided biopsy of a renal tumor. Fifteen sites of NLRP3 gene polymorphisms were identified using the Agena Bioscience MassARRAY platform. The concentrations of the urinary arsenic species were determined by HPLC-HG-AAS. There was a significant dose-dependent association between arsenic and RCC. In addition, six of thirteen NLRP3 alleles, including rs12239046 C, rs10925025 G, rs1539019 C, rs10925026 A, rs10157379 T, and rs12143966 A, had increased odds ratios (ORs) for RCC than other NLRP3 alleles. Among these sites, we found the novel haplotype of five tag-SNPs (C-A-A-A-A) was significantly related to RCC, the OR and 95% confidence interval was 1.44 (1.08-1.92). Furthermore, participants with high total urinary arsenic levels and the NLRP3 rs1539019 C allele had significantly multiplicative and additive interactions for the risk of RCC (p interaction = 0.012). This study is the first to identify the modified effects of NLRP3 risk alleles involved in the association between arsenic and RCC risk in a population with low arsenic exposure.

4.
Radiat Oncol ; 15(1): 72, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252781

RESUMO

BACKGROUND: The optimal adjuvant treatment for stage III endometrial cancer in the era of modern radiotherapy remains undefined. We investigated the benefit of adjuvant radiotherapy for women who underwent optimal resection for stage III endometrial cancer in the era of modern radiotherapy. METHODS: We retrospectively reviewed patients with endometrial cancer who were treated between 2010 and 2018. Adjuvant treatment included radiotherapy by modern radiotherapy techniques (intensity-modulated or volumetric modulated arc radiotherapy), chemotherapy, or both. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed via multivariate Cox proportional hazards models. RESULTS: One hundred sixty-one patients were initially included (52, 9, and 100 with stages IIIA, IIIB, and IIIC cancer, respectively); 154 patients (96%) received adjuvant therapy. Such adjuvant treatment was associated with improved RFS (p = 0.014) and OS (p = 0.044) over surgery alone. Adjuvant radiotherapy by modern radiotherapy techniques led to low incidence of acute (25%) and chronic (7%) grade ≥ 2 gastrointestinal toxicity. On univariate analysis, non-endometrioid histology and grade 3 status were associated with higher risks of tumor recurrence and death, whereas adjuvant radiotherapy alone or in combination chemotherapy reduced their risks. On multivariate analysis, non-endometrioid histology was associated with increased recurrence (hazard ratio [HR], 2.95; p = 0.009), whereas adjuvant radiotherapy alone or with chemotherapy was associated with lower recurrence (HR, 0.62; p = 0.042). Patients > 60 years of age (p = 0.038) as well as those with endometrioid histology (p = 0.045), lymphovascular space invasion (p = 0.031), and ≥ 2 positive lymph nodes (p = 0.044) benefited most from adjuvant radiotherapy. CONCLUSIONS: Modern adjuvant radiotherapy (intensity-modulated or volumetric modulated arc radiotherapy) alone or with chemotherapy should be considered for women with optimally resected stage III endometrial cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04251676. Registered 24 January 2020. Retrospectively registered.


Assuntos
Neoplasias do Endométrio/radioterapia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos Retrospectivos
5.
Urol Oncol ; 38(5): 465-475, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32199754

RESUMO

BACKGROUND: Urothelial carcinomas (UCs) are highly prevalent in patients with end-stage renal disease. Chronic kidney disease (CKD) is the predecessor of end-stage renal disease, and it is also associated with UC. However, the interplay between CKD and UC lacks solid evidence. Acrolein is produced by polyamines and has been suggested to be the uremic "toxin." The level of acrolein correlates well with chronic renal failure. We recently found that acrolein-induced DNA damage and inhibited DNA repair in urothelial cells, which contribute to bladder cancer. Therefore, we hypothesize that acrolein is involved in the formation of UC in patients with CKD. MATERIALS AND METHODS: A total of 62 UC patients and 43 healthy control subjects were recruited. Acrolein-DNA (Acr-dG) adducts and p53 gene mutations in UC tissues, plasma acrolein-protein conjugates (Acr-PC) and S-(3-hydroxypropyl)-N-acetylcysteine levels, and urinary Acr metabolites were analyzed in these patients. RESULTS: Acr-dG levels were statistically correlated with CKD stages in UC patients (P < 0.01). Most p53 mutations were G to A and G to T mutations in these patients, and 50% of mutations at G:C pairs occurred in CpG sites, which is similar to the mutational spectra induced by Acr-dG adducts. Acr-PC levels in the plasma of UC patients with CKD were significantly higher than those of control subjects (P < 0.001). Altered urinary S-(3-hydroxypropyl)-N-acetylcysteine was also found in UC patients with CKD compared to control subjects (P < 0.005). CONCLUSION: These results indicate that acrolein acts as an endogenous uremic toxin and contributes to UC formation in patients with CKD.

6.
Cancer Med ; 9(7): 2372-2378, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32027096

RESUMO

Anoctamins were originally identified as a family of calcium-activated chloride channels, but recently their roles in the development of different types of malignancies were suggested. Here, we evaluated the associations between 211 common single-nucleotide polymorphisms in 10 anoctamin genes with biochemical recurrence (BCR) after radical prostatectomy (RP) for localized prostate cancer. Four SNPs (ANO4 rs585335, ANO5 rs4622263, ANO7 rs62187431, and ANO10 rs118005571) remained significantly associated with BCR after multiple test correction (P < .05 and q = 0.232) and adjustment for known prognostic factors. Expression quantitative trait loci analysis found that ANO5 rs4622263 C and ANO10 rs118005571 C alleles were associated with decreased mRNA expression levels. Moreover, lower expression of ANO5 was correlated with more advanced tumors and poorer outcomes in two independent prostate cancer cohorts. Taken together, ANO5 rs4622263 was associated with BCR, and ANO5 gene expression was correlated with patient prognosis, suggesting a pivotal role for ANO5 in prostate cancer progression.

7.
Cancer Genomics Proteomics ; 17(2): 209-216, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32108043

RESUMO

BACKGROUND/AIM: This study aimed to identify the genes that cause biochemical recurrence (BCR) following radical prostatectomy (RP) in men with localized prostate cancer. PATIENTS AND METHODS: A two-stage genetic association study of 19 single-nucleotide polymorphisms in 11 key cell cycle regulation genes was carried out. BCR-free survival after RP was evaluated in a discovery cohort of 458 patients with prostate cancer, and replication was investigated in another cohort of 185 patients. RESULTS: A consistent association was found between BCR and rs2290291 (discovery: p=0.008; replication: p=0.029). rs2290291 is located in the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ), and was predicted to possess a regulatory function that affected YWHAZ expression. Furthermore, YWHAZ expression was frequently up-regulated in advanced tumours, and associated with poorer survival in patients with prostate cancer. CONCLUSION: YWHAZ rs2290291 was found to be associated with BCR. YWHAZ may function as a putative oncogene during prostate cancer progression.

8.
J Formos Med Assoc ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32081564

RESUMO

BACKGROUND/PURPOSE: The inflammatory milieu has been firmly established to affect cancer progression. However, the connection between natural killer (NK) cells and prostate cancer (PCa) has not been elucidated. METHODS: Prospective data on NK cell activity (NKA) and NK cell subset distribution patterns were evaluated from 51 patients treated with robot-assisted laparoscopic radical prostatectomy. Whole-blood samples were collected from patients preoperatively and 4-6 weeks postoperatively. The samples were subjected to NKA tests, NK cell number counts, determination of the NKG2D (activating receptor of NK cells), NKG2A (inhibiting receptor), and other surface markers. All the analyses were compared to the clinicopathological characteristics of patients. NKA was estimated by measuring interferon-γ (IFN-γ) levels after stimulation of the peripheral blood with PROMOCA™, which specifically stimulates the release of IFN-γ from NK cells. RESULTS: NKA was lower in patients with PCa than in healthy participants (484.66 vs. 1550 pg/mL). A paired comparison revealed significantly higher NKA postoperatively than preoperatively (1054 vs. 484.66 pg/mL; p = 0.011). Patients with negative surgical margins exhibited significantly higher postoperative NKA and NKA ratio (postoperative NKA/preoperative NKA) than those with positive margins (557 vs. 1921 pg/mL, p < 0.001; 3.6 vs. 1.59, p = 0.024). However, there was no difference in the postoperative NK cell number or the CD56bright/CD16-/CD3- or CD56dim/CD16+/CD3- cell numbers between the negative and positive margin groups. Postoperative NKA was significantly higher in lower-stage (1/2) than in higher-stage (3/4) PCa (1365 vs. 594 pg/mL, p = 0.014). CONCLUSION: NKA was significantly higher postoperatively than preoperatively. Patients with positive surgical margins had lower postoperative NKA than those with negative margins. Lower postoperative NKA was also observed in higher-stage PCa. NKA could be used as a supplemental marker for detecting the remaining tumor cells after prostatectomy in combination of PSA.

9.
Medicine (Baltimore) ; 99(7): e18842, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049786

RESUMO

Acute urinary retention (AUR) is associated with hormone imbalance in men. However, limited studies focused on exploring the complications of AUR in patients with prostate cancer (PC) who receive androgen deprivation therapy (ADT). Therefore, we aim to evaluate the subsequent risk of AUR in ADT-treated PC patients. We collected data from 24,464 male patients who were newly diagnosed with prostate malignancy from a longitudinal health insurance database of catastrophic illness in 2000 to 2008. All PC patients were categorized into 2 cohorts, namely, ADT cohort and non-ADT cohort, based on whether or not the patient receives ADT. The patients were followed up until the occurrence of AUR. Multivariate Cox proportional hazard regression and Kaplan-Meier analysis were performed. After a 12-year follow-up, the incidence rates of AUR were 12.49 and 9.86 per 1000 person-years in ADT and non-ADT cohorts, respectively. Compared with the non-ADT cohort, the ADT cohort had a 1.21-fold increase in AUR risk based on the adjusted model (95% CI = 1.03-1.43). In addition, PC patients receiving early ADT treatment within 6 months or receiving only luteinizing hormone-releasing hormone treatment also had significantly increased risk of AUR. ADT was positively associated with AUR risk. PC patients receiving ADT should be informed about the risks of bladder outlet obstruction and AUR, and they may benefit from screening for related risk factors. New guidelines and treatments should be proposed in the future to manage ADT-related lower urinary tract symptoms and reduce the risk of AUR.


Assuntos
Antagonistas de Androgênios/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Retenção Urinária/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Estudos de Casos e Controles , Humanos , Incidência , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taiwan/epidemiologia , Retenção Urinária/induzido quimicamente
10.
J Xray Sci Technol ; 28(1): 111-124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31904003

RESUMO

BACKGROUND: Extended-field (EF) bone marrow-sparing (BMS) radiotherapy is attracting interest for cervical cancer patients with para-aortic lymphadenopathy. OBJECTIVE: To compare dosimetric quality of volumetric-modulated arc therapy (VMAT) vs. helical tomotherapy (HT) during EF BMS radiotherapy. METHODS: HT dose-volume histogram parameters including (1) coverage, homogeneity, and conformity of target volumes, (2) sparing of organs-at-risk, (3) monitor units, and (4) estimated treatment time were compared with those of VMAT in 20 cervical cancer patients who underwent EF BMS radiotherapy. The pelvic and para-aortic regions received 45-Gy dose (25 fractions), with simultaneous integrated boost of 55 Gy (25 fractions) for pelvic and para-aortic lymphadenopathy, followed by a parametrial boost of 9 Gy (5 fractions). RESULTS: The HT-based and VMAT techniques achieved adequate and similar target volume coverage with good dose homogeneity and conformity, while sparing all organs-at-risk, including the rectum, bladder, bowel, bone marrow, femoral head, kidney, and spinal cord. The HT treatment plan had significantly higher monitor units (p < 0.001) and longer estimated treatment times (p < 0.001). CONCLUSIONS: VMAT and HT plans are suitable for EF BMS radiotherapy, which can achieve adequate target volume coverage while sufficiently sparing normal tissue. In addition, VMAT, compared to HT planning, yielded shorter estimated treatment times.

11.
Cancer Epidemiol ; 64: 101657, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918180

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) remains the mainstay treatment for locally advanced or metastatic prostate cancer (PC). However, potential effects of ADT treatment on neurocognitive dysfunction remain unclear. The present study was conducted to assess the relation between ADT treatment and risk of cognitive decline in Asian men with PC. METHODS: A population-based cohort of 24,464 men with PC, each newly diagnosed between 2000 and 2008, was selected from the Taiwan National Health Insurance Database. Subjects were further grouped by treatment as non-ADT (n = 4685) or ADT (n = 12,740), members of the latter subjected to bilateral orchiectomy or medical treatment (ie, luteinizing hormone-releasing hormone agonists, antiandrogens, or combination therapy). A multivariable Cox proportional hazard model with ADT as time-dependent covariate was used to generate adjusted hazard ratios (HRs) of subsequent cognitive decline, including dementia, Alzheimer's disease (AD), and Parkinson's disease (PD). RESULTS: ADT showed a significant association with overall risk of cognitive decline (HR = 1.51, 95 % CI: 1.31-1.74), especially for PD, dementia, and non-Alzheimer dementia (non-AZD). When stratified by various ADT regimens, antiandrogen-only recipients displayed significantly heightened risks of subsequent AD, non-AZD, and PD. However, combined androgen blockade also imposed an increased risk of PD. There was no apparent correlation between duration of ADT exposure and cognitive dysfunction. CONCLUSIONS: Various ADT therapies may have disparate impacts on cognitive function. Prospective studies exploring pertinent clinical characteristics more fully are needed to confirm these findings.

12.
Sci Rep ; 10(1): 776, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964956

RESUMO

To evaluate the predictive accuracy of the %p2PSA and prostate health index (PHI) in predicting aggressive pathological outcomes in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP), we enrolled 91 patients with organ-confined PCa who were treated with robot-assisted RP. p2PSA levels and the PHI were investigated for their ability to predict pathological results. The %p2PSA and PHI were both significantly higher in patients with ≥pT3 disease, high-risk disease, positive surgical margin, or seminal vesical invasion (SVI). In univariable analysis, p2PSA derivatives were significant predictors of the presence of ≥pT3 disease, high-risk disease, positive surgical margin, and SVI. To predict adverse pathological outcomes at a sensitivity of 90%, p2PSA derivatives had higher specificity than standard PSA derivatives. In multivariable analysis, additional increases in the area under the receiver operating characteristic curve (AUC) were observed with the %p2PSA and PHI for ≥pT3 disease, high-risk disease, and positive surgical margin (8.2% and 2.7%, 6.2% and 4.1%, and 8.6% and 5.4%, respectively). A PHI ≥61.26 enhanced the predictive accuracy of the model for SVI by increasing the AUC from 0.624 to 0.819 (p = 0.009). The preoperative %p2PSA and PHI accurately predict adverse pathological results and are useful for decision-making.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31783478

RESUMO

Cluster of differentiation (CD) antigens are cell surface markers used to differentiate haematopoietic cell types. These antigens are present in various malignancies and are reportedly linked to patient prognosis; however, they have not been implemented as prostate cancer progression markers. Here, we aimed to assess the impact of genetic variation in haematopoietic cell CD markers on clinical outcomes in patients with prostate cancer. An association study of 458 patients with prostate cancer was conducted to identify single-nucleotide polymorphisms in 11 candidate CD marker genes associated with biochemical recurrence (BCR) after radical prostatectomy. Identified predictors were further evaluated in an additional cohort of 185 patients. Joint population analyses showed that CD1B rs3181082 is associated with BCR (adjusted hazard ratio 1.42, 95% confidence interval 1.09-1.85, p = 0.010). In addition, rs3181082 overlapped with predicted transcriptional regulatory elements and affected CD1B expression. Furthermore, low CD1B expression correlated with poorer BCR-free survival. Our results indicated that CD1B rs3181082 confers prostate cancer progression and may help improve clinical prognostic stratification.


Assuntos
Antígenos CD1/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Neoplasias da Próstata/genética
14.
J Clin Med ; 8(11)2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31766169

RESUMO

The aim of this study was to investigate prognostic molecular targets for selecting patients with muscle-invasive bladder cancer undergoing bladder-preserving therapy. Pretreatment biopsy samples from patients with muscle-invasive bladder cancer receiving trimodality bladder-preserving therapy were analyzed for expression levels of p53, p16, human epidermal growth factor receptor-2 (Her-2), epidermal growth factor receptor (EGFR), nuclear factor-kappa B (NFκB; p65), E-cadherin, matrix metalloproteinase-9 (MMP9), meiotic recombination 11 homolog (MRE11), programmed death-1 ligand (PD-L1), and mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemical (IHC) staining. The correlations between these molecular markers with local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and overall survival (OS) were explored. Biopsy samples from 41 out of 60 patients were evaluated using IHC. Univariate analysis revealed that the high expression of NFκB is associated with significantly worse LPFS, DMFS, and OS, and low expression of p16 is associated with significantly lower LPFS. Upon further multivariate analysis including sex, age, stage, and selected unfavorable factors in the model, NFκB and p16 independently remained significant. The investigational in vitro study demonstrated that irradiation induces up-regulation of NFκB signaling. Irradiated bladder cancer cells showed increased invasion capability and clonogenic survival; inhibition of NFκB signaling by an NFκB inhibitor, SC75741, or RNA interference reversed the observed increases. NFκB expression (p65) is associated with prognostic significance for both LPFS and DMFS in patients treated with bladder-preserving therapy, with consistent impact on cell viability of bladder cancer cells. NFκB may be a putative molecular target to help with outcome stratification.

15.
Sci Rep ; 9(1): 14231, 2019 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578427

RESUMO

This study aimed to investigate the risks of thromboembolic vascular disease following androgen deprivation therapy (ADT) administered to prostate cancer (PCa) patients. A total of 24,464 men with newly diagnosed PCa during 2000-2008 were recruited through a longitudinal health insurance database in Taiwan. All PCa patients were stratified into two: ADT and non-ADT groups. Patients with ADT treatment were grouped into three: surgical castration, chemical castration, and anti-androgen alone. The risks of pulmonary embolism (PE), peripheral arterial occlusion disease (PAOD), and deep vein thrombosis (DVT) were assessed in multiple Cox proportional-hazards regression with time-dependent covariates. During the 12-year follow-up period, incidence rates per 1000 person-years in ADT and non-ADT groups were 2.87 and 1.62 for DVT, 1.00 and 0.52 for PE, and 1.03 and 0.70 for PAOD, respectively. The DVT and PE risks were significantly increased in patients receiving combined androgen blockade (CAB) compared with the counterpart ADT non-recipients. After adjusting for potential risk factors, PCa patients receiving CAB had the highest PE risk (HR = 3.11), followed by DVT risk (HR = 2.53). The DVT risk remained elevated throughout the entire duration of chemical castration. However, high PE risk was observed in patients with ≤720-day treatment duration. No association was found between ADT and PAOD risks. Overall, the risks of PE and DVT were considerably heightened in Asian men subjected to CAB for PCa, whereas PAOD risk was unrelated to such treatments.

16.
Sci Rep ; 9(1): 9489, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263127

RESUMO

In this study, we investigated post-orchiopexy testicular growth of undescended testes (UDTs) at different primary locations and determined the risk factors for testicular atrophy (TA). We conducted a retrospective chart review of boys who had undergone orchiopexy for UDTs during January 2001-December 2013. Patient profile, age at operation, primary UDT location, and testicular volume were noted. TA was defined as ≥50% loss of volume after orchiopexy. The primary endpoints were testicular growth and TA after orchiopexy. The secondary endpoint was risk factors for TA. In total, 182 boys had undergone regular ultrasonography; the median follow-up period was 34 months. Among 230 UDTs, 18 (7.8%) atrophic testicles were identified within a median interval of 13 months after orchiopexy. TA rates were 3.3% (1/30), 6.9% (12/173), and 18.5% (5/27) in primary suprascrotal, canalicular, and above-inguinal UDTs, respectively. The survival probability of UDT was 91%, 92% and 100% when orchiopexy was performed in age ≤1 year, 1 < age ≤2 years, and 100% in age >2 years, respectively. Multivariate analysis revealed that inguinal and above-inguinal UDTs (hazard ratio [HR] 11.76, 95% confidence interval [CI] 1.55-89.33, p = 0.017) and genetic or endocrine disorders (HR 3.19, 95% CI 1.19-8.56, p = 0.021) were the risk factors for TA, but not age at operation, premature birth, and laterality. Thus, TA incidence was higher when patients had high primary testicular locations. Early orchiopexy before two years of age may be associated with higher TA risk, while most testicles have promising growth after orchiopexy.

17.
Cell Death Dis ; 10(6): 420, 2019 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142735

RESUMO

Accelerated glucose metabolism is critical in hepatocarcinogenesis, but the utilities of different glucose transporter inhibitors in treating hepatocellular carcinoma (HCC) remain largely uncharacterized. In this study, we examined a collection of glucose transporter inhibitors and found differential anti-HCC effects among these compounds. Canagliflozin (CANA), phloretin, and WZB117 decreased cellular glucose influx, but only CANA showed potent growth inhibition in HCC, which indicated a glucose-independent anti-HCC mechanism. Notably, we found that CANA treatment significantly downregulated the expression of ß-catenin in HCC cells in. By co-treating cells with cycloheximide and MG-132, we proved that CANA promoted proteasomal degradation of ß-catenin protein by increasing phosphorylation of ß-catenin, and CANA-induced inactivation of protein phosphatase 2A was identified being responsible for this effect. Moreover, using Huh7 xenografted tumor model, CANA treatment was shown to delay tumor growth and improved the survival of HCC bearing mice. Our study highlights the unique dual ß-catenin-inhibition mechanisms of CANA, which may provide new thoughts on treating HCC patient with concurrent diabetes, and, furthermore, on developing novel treatment targeting metabolic reprogram and/or WNT/ß-catenin signaling in HCC.

18.
Cancer Cell Int ; 19: 87, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30996687

RESUMO

Background: To determine the association between circadian pathway genetic variants and the risk of prostate cancer progression. Methods: We systematically evaluated 79 germline variants in nine circadian pathway genes in a cohort of 458 patients with localized prostate cancer as the discovery phase. We then replicated the significant findings in another cohort of 324 men with more advanced disease. The association of each variant with prostate cancer progression was evaluated by a log-rank test and Cox regression. Results: A single nucleotide polymorphism of the neuronal PAS domain protein 2 (NPAS2) gene (rs6542993 A>T) was found to be associated with a significantly higher risk of disease progression in both localized (P = 0.001) and advanced (P = 0.039) prostate cancer cases. In silico analysis revealed decreased expression levels of NPAS2 in carriers of the T allele of rs6542993 compared with those carrying the A allele. Consistently, downregulation of NPAS2 expression was associated with more aggressive prostate cancer and poor progression-free survival (log-rank P = 0.002). Conclusions: The NPAS2 rs6542993 polymorphism may be a promising biomarker, and may shed light on the pathways that govern prostate cancer progression.

19.
Cancer Med ; 8(6): 2777-2783, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30993852

RESUMO

The aberrant expression of cell adhesion molecules is a hallmark of epithelial-to-mesenchymal transition, resulting in the transformation of cancer cells to a more aggressive phenotype. This study investigated the association between genetic variants in cell adhesion pathways and the prognosis of patients with prostate cancer following radical prostatectomy (RP). A total of 18 haplotype-tagging single-nucleotide polymorphisms (SNPs) in eight cancer-related adhesion molecules were genotyped in 458 prostate cancer patients, followed by the replication of the top SNPs in an additional set of 185 patients. Log-rank test and multivariate Cox regression analysis adjusted for covariates were used to evaluate associations with the risk of biochemical recurrence (BCR) after RP. In the discovery set, four SNPs in CDH2 were marginally associated with BCR. Among these, CDH2 rs643555C > T was found to be associated with BCR in the replication set. Patients with rs643555TT genotype had a significantly shorter BCR-free survival compared with those with CC/CT genotypes in the combined analysis (adjusted hazard ratio 1.78, 95% confidence interval 1.19-2.67, P = 0.005). Additional analyses revealed that rs643555T was associated with higher expression of CDH2, and upregulated CDH2 was correlated with tumor aggressiveness and shortened BCR-free survival. In conclusion, rs643555C > T affects CDH2 expression, and thus influences BCR in localized prostate cancer patients treated with RP. CDH2 rs643555 may be a promising biomarker to identify patients at high risk of poor prostate cancer prognosis.

20.
J Formos Med Assoc ; 118(1 Pt 2): 260-267, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29779925

RESUMO

BACKGROUND/PURPOSE: Prostate specific antigen (PSA) with low specificity that causes unnecessary prostate biopsies increases clinical morbidities, psychological stress, and medical expenses. We aimed to test the accuracy and cutoff value of Prostate Health Index (PHI) in men for prostate cancer detection. METHODS: We prospectively enrolled 213 men who underwent prostate biopsy with PSA≦10 ng/ml or abnormal findings on digital rectal examination. Total PSA (tPSA), free PSA (fPSA) and p2PSA levels were measured by serum samples before prostate biopsy. PHI was calculated as (p2PSA/fPSA) × âˆštPSA. Multivariable logistic regression analyses were used to predict the risk of cancer and detect clinically significant prostate cancer. RESULTS: 33 (27.0%) patients were confirmed with the diagnoses of prostate cancer by prostate biopsy. The levels of p2PSA, %p2PSA, and PHI showed statistically significant differences between prostate cancer patients and non-cancer patients. %p2PSA and PHI had the highest area under the receiver operating characteristic curve (AUC) of 0.723 and 0.772 (both p < 0.001), respectively, predicting cancer detection at biopsy than other predictors (tPSA, fPSA, %fPSA, and PSA density (AUC: 0.544, 0.538, 0.593, and 0.664, respectively). In multivariable logistic regression, %p2PSA had a statistical significant odds ratio 8.51 (p = 0.003) and PHI had an odds ratio with marginal significance 4.18 (p = 0.06). CONCLUSION: %p2PSA and PHI increased the diagnostic accuracy with significantly greater sensitivity and specificity than tPSA. We determined an optimal cut-off value of PHI among Taiwanese population. These findings support the usefulness in the decisional process of prostate biopsy.


Assuntos
Antígeno Prostático Específico/sangue , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Idoso , Biomarcadores Tumorais/sangue , Biópsia/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Estudos Prospectivos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Curva ROC , Taiwan
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